期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 7, 页码 4214-4221出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.7.4214
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资金
- NCI NIH HHS [CA 21765] Funding Source: Medline
- NIAID NIH HHS [AI 39480] Funding Source: Medline
- NIDDK NIH HHS [DK 59778, DK 63363] Funding Source: Medline
TNF-alpha converting enzyme (TACE; ADAM17), a member of the ADAM (a disintegrin and metalloprotease) family of metalloproteases, has been shown to cleave a wide variety of cell surface proteins of immunological importance. Due to the broad expression of TACE and the early postnatal lethality of TACE-deficient mice, it has been difficult to assess the role of TACE in lymphocyte development. Indeed, it is not known whether hemopoietic and/or nonhemopoietic expression of TACE is required for normal lymphocyte development. In the current study, we analyzed the lymphoid system of tace(Delta 5Zn/Delta Zn) mice and tace(Delta Zn/Delta Zn) bone marrow RAG1(-/-) recipients. Our results clearly show that nonlymphocyte expression of TACE is required for normal lymphocyte development and lymphoid organ structure. Lack of TACE function resulted in a partial block in T cell development at the double-negative 4:double-positive transition in the thymus, a loss of B cell development/maturation in the spleen, and a lack of B cell follicle and germinal center formation in the spleen. Thus, TACE serves as a lymphocyte extrinsic factor that is essential for normal T development and peripheral B cell maturation.
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